Similar to other chronic viral infections, infection of an individual with a second viral strain (dual infection), also occurs in HIV infection. This proposal aims to determine: (1) novel methods of detecting intraclade dual infection, (2) the incidence and prevalence of dual infection (both coinfection and superinfection) among recently and chronically HIV infected individuals, and (3) the clinical and virologic correlates of dual infection. This proposal is based on a collaboration with the Acute Infection Early Disease Research Program (AIEDRP) network and the San Diego site of the Early Intervention Program (EIP). At UCSD we have available samples from 292 eligible participants from 7 AIEDRP sites for a total of 1224 well-characterized longitudinal samples. From EIP we conservatively estimate to enroll 140 participants over the two years of the study and ultimately have 320 timepoint samples available for dual infection screening. Using new methods for screening, we estimate to identify 55 instances of intraclade dual infection. Demographic and clinical data will also be available from the AIEDRP and EIP cohorts and will be used to determine the correlates associated with intraclade dual infection. We will also generate sequence data from blood samples available from participants identified with dual infection to characterize the virologic processes following dual infection, such as recombination. While not completely analogous to vaccination, the identification and characterization of intraclade dual infections represent a unique opportunity to learn how and why a sensitized immune system fails to protect its host from infection by a very closely related second HIV strain. We project that we will identify and characterize by far the largest cohort of intraclade dual infections reported to date. PUBLIC HEALTH RELEVANCE: Recently, it was discovered that individuals can be infected with HIV more than once. This is often called re-infection or dual infection. We aim to develop new methods for detecting when dual infection has occurred, how often dual infection occurs in a large clinical cohort of people with HIV infection, what are the clinical consequences of HIV dual infection, and evaluate how the two different viral strains interact with each other in the same person following dual infection.